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Faster Healing for Severe Fractures

A new surgical procedure can repair severe bone injuries and defects more quickly and simply than current methods, which include bone-grafting operations and lengthening procedures that involve inserting pins through the skin to pull bones together.

New bone: An x-ray image of a patient who had a leg lengthened using the new surgical method. This image was taken after six months, showing a healed bone.

The new technique makes use of a thin tissue called the periosteum, which lines the outer surface of all bones and contains stem cells that develop into bone to repair damage. To repair major bone breaks, or repair serious defects, the researchers use the periosteum as a sleeve placed around a missing section of bone to encourage bone regrowth. For cases where there is not enough periosteum, the researchers have developed an artificial membrane as a substitute.

Melissa Knothe Tate, a professor of biomedical engineering at Case Western Reserve University in Cleveland, and her husband, Ulf Knothe, an orthopedic surgeon at the Cleveland Clinic, have successfully tested their method on a wheelchair-bound patient who needed surgery to lengthen one of her legs. They’ve also successfully tested it on sheep. The researchers presented their work yesterday at the Orthopedic Research Society meeting in New Orleans.

In the new procedure, carried out on the wheelchair patient, the researchers made a small vertical incision in the periosteum near to where a large piece of bone was missing after the leg had been lengthened. They then peeled the periosteum back, so that it remained attached to the blood vessels on the outside, and cut away a piece of bone beneath, which was then used to plug the large gap in the leg bone. The periosteum was sutured closed, forming a sleeve around the section from which the bone was removed. The gap was repaired by the transplanted segment of bone while cells from the sutured periosteum infiltrated the space below it and turned into new bone. The patient saw new bone growth one month after surgery. Knothe Tate says that such a defect would normally not heal without more serious surgery.

One of the most common methods for treating a severe bone injury is to take bone from a non-weight-bearing area like the hip and graft it onto the injured site, but that can leave the site the bone was taken from at risk of a fracture. Jennifer Elisseeff, a biomedical engineer at Johns Hopkins University, says very little can be done to fix large gaps in bone, but adds that the new technique “will have a significant effect for healing fractures.”

Norman Marcus, an orthopedic surgeon at the Virginia Cartilage Institute, in Springfield, VA, says artificial treatments fall into two categories: structural and growth-related. Structural products, typically called bone fillers, can be made of items like coral and calcium phosphate. Growth-related products, which are usually in the form of powders and gels, are used to stimulate bone growth. While the growth promoters are more effective, they are expensive, says Marcus.

Slicing and dicing: This illustration shows how a section of bone with a tumor (very top) can be removed (A), leaving a gap in the bone. The periosteum is then cut and peeled back (B), but remains intact. The bone underneath is then moved down (C) to fill the gap, and the periosteum is sutured around the area where the bone was removed.

The researchers have also created an artificial periosteum sleeve, which they tested in sheep, for bone injuries where there is not enough tissue available. The artificial membrane was seeded with collagen; a mixture of collagen and periosteal cells taken from a particular sheep; or pieces of periosteum from the patient’s surrounding bone. The researchers wrapped the sleeve around the injured area and sewed it on like a patch. They found that the sheep given the periosteum alone experienced the fastest repair, with new bone growth two to three weeks after surgery.

The work “combines tissue engineering approaches with surgical intervention and leverages the natural ability for repair,” says Elisseeff.

One problem is that stem cells can differentiate into different things like tendons, cartilage, or bone, says Marcus. The researchers showed that the stem cells in the periosteum were coaxed into becoming bone by mechanical stress. For instance, in the sheep experiments, the mechanical cues happen naturally when the sheep shift their weight.

“There are lots of experimental techniques but few clinical methods, and if this has been successful in patients, that is where the real breakthrough will be,” says Farshid Guilak, a professor of orthopedic surgery and director of the Orthopaedic Bioengineering Laboratory at Duke University Medical Center.

“This is very important progress,” adds Yunzhi Yang, an assistant professor at Houston Biomaterials Research Center at the University of Texas Health Science Center in Houston.

Knothe Tate says the plan is to license the technology to companies by the end of the year, and says there are a couple of “major players” interested. “We want to provide a cheap alternative that can be widely used in the field,” she says.

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